Autism spectrum disorder (AS) includes three separate diagnoses, which include autism, Asperger's syndrome and Pervasive Developmental Delay (PDD). PDD is characterized by developmental delays of sociability, communication and use of imagination. Asperger's syndrome is a more severe form of PDD but lacks the language and intelligence deficits normally associated with autism. Autism is exemplified by severe communication impairments, social interaction deficits and repetitive/stereotypic behaviors. Each of these disorders has specific diagnostic criteria as outlined by the American Psychiatric Association (APA) in its Diagnostic & Statistical Manual of Mental Disorder's (DSM-IV-TR).
Autism impacts the normal development of the brain in the areas of social interaction and communication skills. Children and adults with autism typically have difficulties in verbal and non-verbal communication, social interactions, and leisure or play activities.
There is no known single cause for autism, but it is generally accepted that it is caused by abnormalities in brain structure or function. Brain scans show differences in the shape and structure of the brain in autistic versus non-autistic children. Links between heredity, genetics and medical problems have been analysed. In many families, there appears to be a pattern of autism or related disabilities, further supporting a genetic basis to the disorder. While no one gene has been identified as causing autism, it appears that some children are born with a susceptibility to autism.
It has also been suggested that under certain conditions, a number of genes with altered levels or functions may interfere with brain development resulting in autism. On the other hand, certain developmental genes may be associated with autism, including the Wnt2 and reelin genes (Wassink, et al. (2001) Am. J. Med. Genet. 105:406-413; Persico, et al. (2001) Mol. Psychiatry. 6:150-159). Pregnancy or delivery as well as environmental factors such as viral infections, metabolic imbalances, and exposure to environmental chemicals have also been implicated.
Autism tends to occur more frequently than expected among individuals who have certain medical conditions, including Fragile X syndrome, tuberous sclerosis, congenital rubella syndrome, and untreated phenylketonuria (PKU). Some harmful substances ingested during pregnancy also have been associated with an increased risk of autism. In 2002, The Agency for Toxic Substances and Disease Registry (ATSDR) prepared a literature review of hazardous chemical exposures and autism and found no compelling evidence for an association; however, literature in this area was limited.
The question of a relationship between vaccines and autism continues has been debated. In a 2001 investigation by the Institute of Medicine, a committee concluded that the “evidence favors rejection of a causal relationship . . . between MMR vaccines and autistic spectrum disorders (ASD).” The committee acknowledged, however, that “they could not rule out” the possibility that the MMR vaccine could contribute to ASD in a small number of children. While other researchers agree the data does not support a link between the MMR and autism.
Whatever the cause, it is clear that children with autism and PDD are born with the disorder or born with the potential to develop it. Autism is not a mental illness. Children with autism are not unruly kids who choose not to behave. Furthermore, no known psychological factors in the development of the child have been shown to cause autism.
There are no medical tests for diagnosing autism. An accurate diagnosis must be based on observation of the individual's communication, behavior, and developmental levels. However, because many of the behaviors associated with autism are shared by other disorders, various medical tests may be ordered to rule out or identify other possible causes of the symptoms being exhibited.
A brief observation in a single setting cannot present a true picture of an individual's abilities and behaviors. Parental and other caregivers' input and developmental history are very important components of making an accurate diagnosis. At first glance, some persons with autism may appear to have mental retardation, a behavior disorder, problems with hearing, or even odd and eccentric behavior. To complicate matters further, these conditions can co-occur with autism. However, it is important to distinguish autism from other conditions, since an accurate diagnosis and early identification can provide the basis for building an appropriate and effective educational and treatment program.
Research indicates that early diagnosis is associated with dramatically better outcomes for individuals with autism. The earlier a child is diagnosed, the earlier the child can begin benefiting from one of the many specialized intervention approaches.
Accordingly, what is needed is a genetic marker to assess a subject's susceptibility to autism or a disease or disorder related thereto. Also needed is a genetic marker to diagnose autism, and the development of potential drugs or agents that have applications in treating autism or a disease or disorder related thereto, such as Asperger's Disorder or PDD.
The present invention addresses the unmet need for the identification of an autism susceptibility locus and the uses for early diagnostic and prognostic purposes.